Goals for representing knowledge (outline)
• Make things (articles, genes,
antibodies, etc.) easier to find
• Answer questions
• Generate hypotheses
Controlled vocabularies (MeSH)
Ontologies (Gene Ontology)
knowledge graphs on the Web:
the SPARQL query language
knowledge plus computation =
inference, the ABC model
“Ontology”
• The word comes from philosophy:
• “the branch of metaphysics dealing with the nature of being”
• In practice they are:
• A set of concepts, definitions and inter-relationships.
• (The dividing line between “controlled vocabulary”, “thesaurus”, “ontology” is
hazy and not terribly important for practical purposes.)
• We have hundreds of ontologies in biology, e.g. see:
• http://www.obofoundry.org (100+)
• http://bioportal.bioontology.org (500+)
The Gene Ontology
Ashburner et al., Nat Genet. 2000 May;25(1):25-9.
Started in 1999
As a collaboration between 3 Model Organism Databases
Slide credit: Mélanie Courtot, Ph.D.
1. Molecular Function
An elemental activity or task or job
• protein kinase activity
• insulin receptor activity
3. Cellular Component
Where a gene product is located
• mitochondrion
• mitochondrial matrix
• mitochondrial inner membrane
2. Biological Process
A commonly recognized series of events
• cell division
The GO branches
Slide credit: Mélanie Courtot, Ph.D.
Knowledge Graphs
• Also called “knowledge bases”
to distinguish them from
databases.
• An integrated collection of
assertions or claims represented
in something that can be
visualized as a graph and is
technically very much like a
database.
RNASeq reads
Gene X is expressed
Drug A caused Gene
X to be expressed
Knowing what to do with
Drug A..
Why Knowledge Graphs?
?
• Answer explicit questions
• Uncover implicit relations
Implicit relations for hypothesis generation
ABC model
Swanson (1986) Fish oil, Raynaud’s syndrome and undiscovered public knowledge
http://muse.jhu.edu/article/403510/pdf
B
A
C
Raynaud’s
Syndrome
Dietary fish oil
• platelet inhibition
• vasodilation
• lower blood viscosity
Co-occurs in an
article with
Co-occurs in an
article with
?
Open Discovery and Closed Discovery
• Open, you don’t know what C or B is (e.g. disease -> ?drug)
• Closed, you know what C is and are looking for B (e.g. disease – why? – drug)
B
A
C
?
Implicit relations for hypothesis generation
ABC model for drug repurposing
B
A
C
drug
disease
genes
Physical
interaction
genetic
association
?
Querying a knowledge graph with SPARQL
• “SPARQL protocol and RDF query
language”
• RDF: Resource Description
Framework (common standard for
storing knowledge graphs)
• A SPARQL query = a partially
completed graph
• ?’s show what you are looking for
• rest constrains the search
http://www.w3.org/TR/rdf-sparql-query/
?disease
Asking for
Constraints
Metformin
treats
Result:
Metformin
Type 2
diabetes
treats
Example question: drug repurposing
“For a given drug, what
diseases might it be
used to treat?”
?drug
?disease
interacts
with
protein
gene
encoded by
genetic
association
treats??
